The health hazards from tobacco smoking are well established. Of the approximately 4,000 by-products of combustion found in cigarette smoke, many of which are known carcinogens, the three substances studied most have been tars, carbon monoxide and nicotine. Tars and carbon monoxide hae been directly implicated in the production or exacerbation of numerous health disorders.
Thus, tars are the causitive agents in cigarette smoke most implicated in the induction of such cancers as lung, larynx, oral cavity, esophageal, bladder, kidney, pancreatic stomach, and uterine and cervix cancers. Tars are also considered responsible for the induction of the hepatic microsomal ensyme systems which result in more rapid deactivation of a variety of drugs such as benzodiazepines as well as anti-depressants and analgesics. Tars are also responsible for the production of bronco pulmonary diseases, including pulmonary emphysema, chronic bronchitis and smokers respiratory syndrome.
Carbon monoxide, a deadly gas, is an important health hazard even in minute quantities because it combines with the hemoglobin in the blood so that the hemoglobin can no longer carry sufficient oxygen. Moreover, the stimulant effect of the nicotine in the smoke causes an increase in cardiac workload and oxygen demand, whereas the carbon monoxide effectly blocks the ability of the heart muscle to capture the needed oxygen. In other words, carbon monoxide and nicotine work together in a synergistically negative manner in a way which often results in anoxia and ultimately in cardiac damage. In addition, carbon monoxide has also been implicated as a causative agent in the development of such disorders as coronary artery disease and atherosclerosis.
Nicotine appears to be the most pharmacologically active substance in tobacco smoke, yet it appears to be not as significant from a health standpoint as the tars and carbon monoxide. However, nicotine is very important from another standpoint, i.e. it is the reinforcing substance in tobacco which maintains the addiction. In this respect, a theme commonly heard among workers in the field of smoking research is, "People would be disinclined to smoke cigarettes if an alternate route of nicotine delivery could be devised."
Several such attempts have been made to administer nicotine in alternate ways, but with varying and generally ineffective results. For example, nicotine-containing pills have been studied; however, effective blood levels of nicotine are not achieved because drugs absorbed in the stomach pass through the liver first where, in this case, 80-90 percent of nicotine deactivation occurs. Similar findings have been demonstrated with nicotine chewing gum although it has been sufficiently successful to warrant its marketing.
There are other long established and traditional ways of absorbing nicotine through the mouth, including chewing tobacco, snuff and the newly introduced products such as "Bandits" which constitute diffusion bags of tobacco, all of such means relying on oral (or nasal) absorption of nicotine through the mucous membrane. However, because of the taste and other sensory effects of tobacco, such a manner of satisfying the nicotine habit is acceptable to only a very limited number of persons. Moreover, these habits still require the utilization of tobacco, and such use remains a problem especially for people with gum, mouth or throat problems as a result of long-term tobacco chewing or snuff "dipping" and who are unable to quit.
With regard to the nicotine gum referred to above, it has produced mouth ulcers in a number of individuals resulting in its rejection. In addition, the nicotine gum produces some gastric absorption with the resultant first pass through the liver and consequent rapid loss of activity. Moreover, first hand reports indicate that some people using the gum rejected it on the basis of taste. Moreover, denture wearers have difficulty with gum in general; this is important as many people who experience the medical problems associated with years of smoking may also be denture wearers.
Nicotine itself has been subjected to considerable study. Nicotine is a liquid alkaloid which is colorless, volatile and strongly alkaline. On exposure to air it turns brown. It is known to be very lipid soluble. The Merck Index, 9th Edition, 1976, page 847, indicates that nicotine base is readily absorbed through mucous membrane and intact skin, but the salts are not. On the other hand, nicotine has no known therapeutic application (The Pharmacological Basis of Therapeutics, fifth edition, Goodman and Gilman, 1970, page 467) and has been primarily used in research as an experimental tool for investigating neural function.
It is known to administer a wide variety of pharmaceuticals transdermally through the skin, and two patents which disclose bandages for administering drugs are the Zaffaroni U.S. Pat. Nos. 3,598,122 and 3,948,254. Drugs indicated to be administerable include anti-microbials sedatives, hypnotics, psychic energizers, tranquilizers, hormones, anti-pyrectics, anti-diabetics, cardovascular agents, anti-spasmatics, anti-malarials, decongestants, nutritional agents, anti-bacterials, antineoplastics, anti-inflammatory agents, desensitizing agents, vaccines, anti-allergics, anti-fungals, anti-perspirants, deodorants, astringents and irritants. Thus, while the field of drugs and pharmaceuticals mentioned in these patents is very wide, there is no disclosure of administration of nicotine; and nicotine appears to have few properties in common with the categories of drugs mentioned in these patents. In view of the fact that nicotine has no therapeutic use, its relationship to any agents mentioned in these patents appears even more remote.
It is further known that the absorption of many topically applied drugs may be enhanced by occlusion, which consists of covering the treated skin with an impermable plastic sheet or film which prevents water evaporation or drug decomposition. Under such circumstances the keratin layer then becomes softer and less effective as a bearer, so that absorption of the drug is facilitated (Annual Review of Medicine, Volume 33, Chapter 18, 1982, "The Principles of Drug Therapy in Skin Disorders", R.C. Heading, pages 475,476).
Insofar as is known, it has not previously been proposed to transdermally administer a drug for the purpose of reducing or eliminating a dependence, or for administering a drug of addiction in a manner that is safer and less damaging than the route by which such drug is normally administered. Insofar as is known, no ganglionic stimulating agent has been previously delivered transdermally, and it is believed that it has not been previously proposed to administer nicotine transdermally.